Researchers have shown that cannabis is not the harmless high the flower-power devotees supposed.

AN ENTIRE generation once turned a blind eye to cannabis use, believing that although the drug was illegal it was also harmless. The depth of this misconception is hitting home as evidence mounts that marijuana can – and does – lead to significant mental health problems.As reported last week in The Australian, the nation’s crumbling mental health services have exposed a disturbing link between cannabis use and a host of behavioural and psychological problems. These range from criminality to psychiatric conditions such as depression and psychosis, a group of disorders including schizophrenia that feature loss of contact with the real world. Think hallucinations, delusions, paranoia and strange shifting moods.

One expert, Paul Dillon – information manager of the National Drug and Alcohol Research Centre at the University of New South Wales – went so far as damning cannabis use as a “time-bomb” threatening today’s generation of young users.

Dillon is not alone in pointing a finger at cannabis. Epidemiologist Wayne Hall – a professor of public health policy at the University of Queensland – says there is “consistent evidence” that regular cannabis users double their risk of psychosis from roughly one in 100, to one in 50.

New and solid support for an increased risk comes from the Christchurch Health and Development study. New Zealanders David Fergusson and his colleagues at the Christchurch School of Medicine are conducting a long-term, or “longitudinal”, study of 1265 New Zealand children. As part of their research, they gathered data on the frequency of cannabis use and psychotic symptoms from 1055 of the participants at ages 18, 21 and 25.

In an interim report published this year in the journal Addiction, the researchers concluded: “The results of the present study add to a growing body of evidence suggesting that regular cannabis use may increase risks of psychosis.” They ruled out the possibility that other unknown factors caused the worrying association they found.

Significantly, Fergusson’s group also excluded the idea – supported by some researchers – that people who develop psychotic symptoms turn to cannabis to relieve their distress, what experts call self-medicating.

“The direction of causality is from cannabis use to psychotic symptoms,” they wrote.

Perhaps more troubling are other recent findings which suggest that young users are at particular risk of eventually suffering psychosis and other mental health problems, claims Hall, co-author of a comprehensive review of the health and psychological effects of cannabis use – conducted for the National Drug Strategy in 2000 – as well as the 2004 update of the review published in the journal Drug and Alcohol Review.

And users, states Hall, are starting earlier and earlier: “Over the last 30 years in Australia the age of starting has dropped. Now the age of initiation is 15 or 16. There’s been a big drop in precocity in a range of behaviours, including alcohol and tobacco use.”

Part of the difficulty facing adolescent users is that today’s cannabis is more potent than yesterday’s marijuana. That’s so, according to Dillon, because people are smoking stronger parts of the plant and doing so in a riskier manner – such as by bong, or waterpipe.

More critically, though, research shows clearly that young brains are at greater risk than mature ones. Although they’ve attained 90 per cent of their adult size, adolescent brains are still growing. They’re “plastic”, subject to extensive internal change, explains Murat Yucel, neuropsychologist at the Melbourne Neuropsychology Centre at the University of Melbourne. “A lot of wiring and rewiring is occurring,” he says. “The brain is being continuously modelled and is maturing right through to the early 20s, especially in the way it is connected.” Yucel adds that areas of the brain integral to regulating emotion and managing memory, along with thinking, are among those still being shaped during adolescence.

According to preliminary findings from brain imaging work that Yucel conducted with colleagues at the Orygen Research Centre – a Melbourne University-based mental health service for people aged 15 to 25 – early cannabis and, to a lesser extent, alcohol use disrupts “wiring” in parts of the brain vital to those key functions. The frontal cortex, hippocampus and amygdala are particularly affected.

It’s far from clear just how dope smoking may impair the formation of healthy wiring. It may be the abundance of receptors – sites on brain cells that respond to connection-busting stimulation by the most active chemical in cannabis, tetrahydrocannabinol, or THC – in the frontal cortex, hippocampus and amygdala.

Alternatively, it may be that problems emerge because the protective sheaths that surround brain cells like surgical gloves are not laid down until the early 20s. “When you introduce cannabis in moderate to high levels (in adolescence) the connections (between brain cells) can be damaged,” Yucel suggests.

But along with Hall and other experts, Yucel argues for a multiplicity of causes, yet to be fully understood. After all, not all young cannabis users are at equal risk of smoking their way to poor brain wiring or psychotic illness. Other variables, from stress to genes, must be cranking up the harm imposed by heavy and early drug use. Right now, that’s precisely what experts worldwide are trying to sort out.

For instance, Yucel and co-workers at Orygen have begun a series of longitudinal studies involving roughly 400 Melbourne students now about 14 years old. They’ve gathered details on the youngsters’ personality, family life and circumstances, and brain biochemistry, with genetic information to come soon.

“As they start using substances and developing various disorders – if they do – we’ll know what kind of (factors) are there and how the onset of mental illness and substance abuse interacted,” explains Yucel.

Meanwhile, scientific attention is focused on a gene called COMT. That’s so because six years ago international collaborators – led by psychiatrist Kieren Murphy, of Ireland’s Dublin Molecular Medicine Centre – discovered that a variation of the gene was associated with psychosis. Tantalisingly, the gene is involved with a brain chemical called dopamine which, in turn, influences how a maturing brain is wired.

Bingo: psychotic symptoms, gene, young brain.

Psychiatrist Avshalom Caspi, of the Institute of Psychiatry at King’s College, London, teamed with David Fergusson and researchers at New Zealand’s University of Otago in Dunedin to unravel the clues. Specifically, they wanted to know if COMT is implicated in the development of psychosis among cannabis smokers.

Again, New Zealanders were central to the quest. This time the 803 young people studied were part of a group of 1037 children whose parents had enlisted them as three-year-olds in the Dunedin Multidisciplinary Health and Development Study, back in the early 1970s. And again, the scientific sleuths collected a suite of physical, genetic and social data, and have followed up the children over the years.

Their verdict on COMT: guilty as charged.

When they looked at the well-being of the participants at age 26, Caspi’s group found that if the young people had begun smoking cannabis in early adolescence, and had the suspect version of COMT, they were 10 times more likely to have experienced psychotic illnesses than people who never smoked. That was even if they had the troublesome version of the gene.

Clearly, cannabis use played a role in the onset of mental disorder, at least for the Dunedin smokers. But as Caspi’s group noted in Biological Psychiatry in April (2005;57:1117-27), “the vast majority of young people who use cannabis do not develop psychosis”. They argue that the whole story remains untold.

Part of the story undoubtedly includes less dramatic elements, ones that are getting lost in the high-profile discussion of genes, psychosis and their ilk. “The serious risk that’s underplayed is the risk of dependence, of getting stuck and finding it hard to quit,” says Hall.

“We have people coming for treatment in their early 30s who’ve been smoking for 12 to 15 years who haven’t seen it as a problem – until they try to stop. It’s pretty much like alcohol in that regard,” he claims Hall.

Complex? Yes. Troubling? Indeed. As psychiatrist Ian Hickie argues in Weekend Health today (see above), it’s time to rethink social attitudes and policy surrounding cannabis use. So what to do? Hall replies: “Certainly the clearest implication (of recent findings) is we should be telling people about risk. No question at all.”

But there’s been so much “disinformation” about and “hypocrisy” regarding cannabis use over the years that young people, in particular, are turned off by shock-horror health warnings and heavy-handed tactics, says Hall. “Getting tough and increasing penalties is likely to be counter-productive.”

Getting it right, putting it in perspective and acknowledging the inconsistency of prevailing attitudes towards all drugs – from cannabis to coffee – may be a useful starting point.

As Ian Hickie suggests, more than one generation should reconsider the realities of reefer madness.